PMID- 25471741
OWN - NLM
STAT- MEDLINE
DCOM- 20151203
LR  - 20181113
IS  - 1756-9966 (Electronic)
IS  - 0392-9078 (Print)
IS  - 0392-9078 (Linking)
VI  - 33
IP  - 1
DP  - 2014 Dec 4
TI  - Blockade of CXCL12/CXCR4 signaling inhibits intrahepatic cholangiocarcinoma 
      progression and metastasis via inactivation of canonical Wnt pathway.
PG  - 103
LID - 10.1186/s13046-014-0103-8 [doi]
LID - 103
AB  - BACKGROUND: Intrahepatic cholangiocarcinoma (IHCC) is the second most frequent 
      primary malignant liver tumor following hepatocellular carcinoma. It is a highly 
      fatal disease and has few therapeutics. The CXC chemokine ligand-12 (CXCL12)/CXC 
      chemokine receptor type 4 (CXCR4) axis has been shown to be involved in 
      tumorgenesis, proliferation, and angiogenesis in a variety of cancers including 
      IHCC. However, its prognostic significance in IHCC is unclear. The purpose of 
      this study was to examine the functional role of CXCR4 in the progression and 
      metastasis of IHCC and explore the underlying mechanism. METHODS: The CXCR4 
      expression, overall survival, and the clinical characteristics including age, 
      sex, differentiation degree, tumor size, vascular invasion, lymph node 
      metastasis, TNM stage, and T stage were analyzed for 122 IHCC patients. Short 
      hairpin RNA (shRNA) against CXCR4 was used to disrupt the CXCL12/CXCR4 signal 
      transduction pathways in IHCC cell lines. In vitro assays, including CCK-8 assay, 
      flow cytometry, and colony formation assay, and in vivo tumor formation assay 
      were utilized to detect the cell phenotype of CXCR4 knockdown cells. Transwell 
      and wound healing assays were used to examine the IHCC cell invasion and 
      migration ability. The Wnt pathway was assessed by Western blot and beta-Catenin/Tcf 
      transcription reporter assay. RESULTS: We demonstrated that CXCR4 expression was 
      closely correlated with IHCC progression and metastasis characteristics. The 
      overall survival of patients with high CXCR4 expression was significantly lower 
      than that of patients with low CXCR4 expression. Furthermore, we showed that the 
      abrogation of CXCR4 had significantly negative influence on the IHCC cell 
      phenotype, including in vitro cell proliferation, cell cycle, colony formation, 
      cell invasion, and in vivo tumorigenicity. In addition, CXCR4 knockdown 
      downregulated Wnt target genes and mesenchymal markers such as Vimentin and Slug. 
      CONCLUSIONS: In conclusion, our result shows that high CXCR4 expression is 
      associated with IHCC progression and metastasis via the canonical Wnt pathway, 
      suggesting that CXCR4 may serve as a promising therapeutic target for IHCC.
FAU - Zhao, Shengqiang
AU  - Zhao S
AD  - Department of Gastroenterology, Shandong Provincial Hospital, Shandong 
      University, Jinan, China. shengqiang.zhao@gmail.com.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Gastroenterology, Shandong Provincial Hospital, Shandong 
      University, Jinan, China. jingwang78@yahoo.com.
FAU - Qin, Chengyong
AU  - Qin C
AD  - Department of Gastroenterology, Shandong Provincial Hospital, Shandong 
      University, Jinan, China. chengyong.qin@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141204
PL  - England
TA  - J Exp Clin Cancer Res
JT  - Journal of experimental & clinical cancer research : CR
JID - 8308647
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Animals
MH  - Bile Duct Neoplasms/genetics/metabolism/mortality/pathology/*therapy
MH  - Biomarkers, Tumor/genetics/*metabolism
MH  - Cell Cycle
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Chemokine CXCL12/*metabolism
MH  - Cholangiocarcinoma/genetics/metabolism/mortality/secondary/*therapy
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Mice, Nude
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - RNA Interference
MH  - *RNAi Therapeutics
MH  - Receptors, CXCR4/genetics/*metabolism
MH  - Time Factors
MH  - Transfection
MH  - *Wnt Signaling Pathway
PMC - PMC4265318
EDAT- 2014/12/05 06:00
MHDA- 2015/12/15 06:00
PMCR- 2014/12/04
CRDT- 2014/12/05 06:00
PHST- 2014/09/16 00:00 [received]
PHST- 2014/11/21 00:00 [accepted]
PHST- 2014/12/05 06:00 [entrez]
PHST- 2014/12/05 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2014/12/04 00:00 [pmc-release]
AID - s13046-014-0103-8 [pii]
AID - 103 [pii]
AID - 10.1186/s13046-014-0103-8 [doi]
PST - epublish
SO  - J Exp Clin Cancer Res. 2014 Dec 4;33(1):103. doi: 10.1186/s13046-014-0103-8.